Scale-Up From the Microbes Perspective

by Mark Warner (Warner Advisors LLC/Biofuels Digest) On a biotechnology project years ago, one of the team members responsible for biological advancement referred to themselves as the microbial organisms “shop steward”, a reference to union representation. While it was somewhat in jest, it did imply that to get the most from the microbe, its needs had to be taken into account. It’s worth looking at scale-up from the perspective of the microbe for some valuable lessons.

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(I)t can be a very competitive world for a microbe at a biotechnology start-up. You are selected for your pedigree, get your genetic modifications, show improved performance to what is available today, and what happens? In many cases you get replaced by an even better version within a short period of time. It is the reality of synthetic biology, the ability to make rapid changes and improve organism performance is great. The hard part for companies is to determine when the achievement is of a level that will be difficult to replicate and worth process development around the organism. There is danger in technical staff getting too emotionally vested in a certain microbe that can be replaced over-night.

You never call or write – when a microbe “graduates” from the synthetic biology side and makes its way into the process development part of the business to determine if it is as valuable as initial testing indicated, it is important to have a feedback loop. Often the biology and scale-up groups of the business do not share enough information, to the point where the staff developing the hopeful microbes, do not know how each one turns out.

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As a base organism is developed more and more, it can often change attributes that were not intended.

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Products that require extraction from the cell are where the issues begin. Factors like ability to deconstruct the cell to access the target compound, while not converting it to a “soup” of cell pieces that requires costly recovery, is a factor that needs to be balanced against metabolic considerations.

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As pilot scale runs can often cost tens of thousands of dollars each, the cost to determine if the next hot microbe is a winner or not can be significant. The feedback cycle of learning what forecasts success at an early stage is critical to optimizing scale-up spending. READ MORE